Non-Mature miRNA-Encoded Micropeptide miPEP166c Stimulates Anthocyanin and Proanthocyanidin Synthesis in Grape Berry Cells.

The phenylpropanoid and flavonoid pathways exhibit intricate regulation, not only influenced by environmental factors and a complex network of transcription factors but also by post-transcriptional regulation, such as silencing by microRNAs and miRNA-encoded micropeptides (miPEPs). VviMYBC2-L1 serves as a transcriptional repressor for flavonoids, playing a crucial role in coordinating the synthesis of anthocyanin and proanthocyanidin. It works in tandem with their respective transcriptional activators, VviMYBA1/2 and VviMYBPA1, to maintain an equilibrium of flavonoids. We have discovered a miPEP encoded by miR166c that appears to target VviMYBC2-L1. We conducted experiments to test the hypothesis that silencing this transcriptional repressor through miPEP166c would stimulate the synthesis of anthocyanins and proanthocyanidins. Our transcriptional analyses by qPCR revealed that the application of exogenous miPEP166c to Gamay Fréaux grape berry cells resulted in a significant upregulation in flavonoid transcriptional activators (VviMYBA1/2 and VviMYBPA1) and structural flavonoid genes (VviLDOX and VviDFR), as well as genes involved in the synthesis of proanthocyanidins (VviLAR1 and VviANR) and anthocyanins (VviUFGT1). These findings were supported by the increased enzyme activities of the key enzymes UFGT, LAR, and ANR, which were 2-fold, 14-fold, and 3-fold higher, respectively, in the miPEP166c-treated cells. Ultimately, these changes led to an elevated total content of anthocyanins and proanthocyanidins.

Fruit Photosynthesis: More to Know about Where, How and Why.

Not only leaves but also other plant organs and structures typically considered as carbon sinks, including stems, roots, flowers, fruits and seeds, may exhibit photosynthetic activity. There is still a lack of a coherent and systematized body of knowledge and consensus on the role(s) of photosynthesis in these "sink" organs. With regard to fruits, their actual photosynthetic activity is influenced by a range of properties, including fruit anatomy, histology, physiology, development and the surrounding microclimate. At early stages of development fruits generally contain high levels of chlorophylls, a high density of functional stomata and thin cuticles. While some plant species retain functional chloroplasts in their fruits upon subsequent development or ripening, most species undergo a disintegration of the fruit chloroplast grana and reduction in stomata functionality, thus limiting gas exchange. In addition, the increase in fruit volume hinders light penetration and access to CO2, also reducing photosynthetic activity. This review aimed to compile information on aspects related to fruit photosynthesis, from fruit characteristics to ecological drivers, and to address the following challenging biological questions: why does a fruit show photosynthetic activity and what could be its functions? Overall, there is a body of evidence to support the hypothesis that photosynthesis in fruits is key to locally providing: ATP and NADPH, which are both fundamental for several demanding biosynthetic pathways (e.g., synthesis of fatty acids); O2, to prevent hypoxia in its inner tissues including seeds; and carbon skeletons, which can fuel the biosynthesis of primary and secondary metabolites important for the growth of fruits and for spreading, survival and germination of their seed (e.g., sugars, flavonoids, tannins, lipids). At the same time, both primary and secondary metabolites present in fruits and seeds are key to human life, for instance as sources for nutrition, bioactives, oils and other economically important compounds or components. Understanding the functions of photosynthesis in fruits is pivotal to crop management, providing a rationale for manipulating microenvironmental conditions and the expression of key photosynthetic genes, which may help growers or breeders to optimize development, composition, yield or other economically important fruit quality aspects.

Constitutive expression of VviNAC17 transcription factor significantly induces the synthesis of flavonoids and other phenolics in transgenic grape berry cells.

VviNAC17 is a grapevine transcription factor activated by ABA. Because ABA has been proposed as the main signal modulating the secondary metabolism in grape berry skins, here we postulated VviNAC17 as a positive regulator of secondary metabolism in grape cells. To validate the hypothesis, VviNAC17 was constitutively and stably overexpressed in grape berry suspension-cultured cells of Gamay Fréaux cv. by Agrobacterium-mediated transformation. Targeted transcriptional analyses by qPCR showed that several genes involved the phenylpropanoid (VviPAL1), stilbenoid (VviSTS1) and flavonoid pathways (VviDFR, VviLAR1, VviANR, VviLDOX, and VviUFGT1), as well as anthocyanin vacuolar transport and accumulation (VviGST4 and VvMATE1) were significantly upregulated in VviNAC17-overexpressing transgenic cells, which translated in the stimulation of a number of enzymatic activities in those pathways. This was the case of phenylalanine ammonia lyase (PAL) and UDP-glucose:flavonoid 3-O-glucosyltransferase (UFGT) that were about 2-fold and 3.5-fold higher in VviNAC17-overexpressing cells than in control cells. VviNAC17-overexpressing cells accumulated significantly higher amounts of anthocyanins, proanthocyanidins, total flavonoids and total phenolics. These findings confirmed that VviNAC17 is an important positive regulator of secondary metabolism in grapevine contributing to the accumulation of important berry quality-related secondary metabolites.

Disease-Specific Vs Non-Specific Questionnaires on Septoplasty Outcomes.

Introduction: Validated questionnaires are a valuable tool in medical practice. The role of septoplasty in improving patients' non-nasal symptoms and their quality of life is still controversial. The aim of this study was to determine the differences in outcome after septoplasty measured by a disease-specific questionnaire vs a general QoL questionnaire. Materials and Methods: A total of 50 patients underwent septoplasty and completed the SNOT-22 and the SF-36v2 questionnaires preoperatively and at 6 months post-op. Pre-op, post-op and variation for each domain in both questionnaires were calculated and compared with a measure of self-reported health transition (Question 2 of SF-36v2) and with the Minimal important difference (MID) for our sample. Results: SNOT-22 scores significantly improved for each specific question and for the total score. SF-36v2 showed a significant improvement in scores for mental domains (Mental Health, Role Emotional, and Vitality) but less so for the physical domains. MID for our sample was 4.2 points. Patients with variations greater than 4.2 in SNOT-22 total score (74%) revealed significantly better variations in Physical Function, General Health, Social Function and Vitality. Conclusions: Validated questionnaires are a fundamental tool for assessing outcomes of commonly performed surgeries in ENT. Disease-specific questionnaire showed improvement in scores for the majority of patients. The general QoL showed improvement only in Mental Domains. This may suggest that the impact of septoplasty in patient's general health might not be significant.

The influence of light microclimate on the lipid profile and associated transcripts of photosynthetically active grape berry seeds.

Lipids and oils determine the quality and industrial value of grape seeds. Studies with legume seeds demonstrated the influence of light on lipid metabolism and its association with seed photosynthesis. Grape berry seeds are photosynthetically active till mature stage, but mostly during the green stage and veraison. The objective of this work was to compare the lipid profiles of seeds from white grape berries (cv. Alvarinho) growing at two contrasting light microclimates in the canopy (low and high light, LL and HL respectively), previously reported to have distinct photosynthetic competences. Berries were collected at three developmental stages (green, veraison and mature) and from both microclimates, and the seeds were analyzed for their lipid profiles in an untargeted manner using liquid chromatography coupled to high resolution mass spectrometry (LCMS). The seed lipid profiles differed greatly among berry developmental stages, and to a lesser extend between microclimates. The LL microclimate coincided with a higher relative levels of fatty acids specifically at mature stage, while the HL microclimate led to an up-regulation of ceramides at green stage and of triacylglycerols and glycerophospholipids at mature stage. The seed transcript levels of four key genes (VvACCase1, VvΔ9FAD, VvFAD6 and VvLOXO) involved in fatty acid metabolism were analyzed using real-time qPCR. The lipoxygenase gene (VvLOXO) was down- and up-regulated by HL, as compared to LL, in seeds at green and veraison stages, respectively. These results suggest that seed photosynthesis may play distinct roles during seed growth and development, possibly by fueling different lipid pathways: at green stage mainly towards the accumulation of membrane-bound lipid species that are essential for cell growth and maintenance of the photosynthetic machinery itself; and at veraison and mature stages mainly towards storage lipids that contribute to the final quality of the grape seeds.

Exogenous Application of Non-mature miRNA-Encoded miPEP164c Inhibits Proanthocyanidin Synthesis and Stimulates Anthocyanin Accumulation in Grape Berry Cells.

Secondary metabolic pathways in grape berries are tightly regulated by an array of molecular mechanisms, including microRNA-mediated post-transcriptional regulation. As recently discovered, before being processed into mature microRNAs (miRNAs), the primary transcripts of miRNAs (pri-miRNAs) can encode for small miRNA-encoded peptides (micropeptides - miPEPs) that ultimately lead to an accentuated downregulation of the respective miRNA-targeted genes. Although few studies about miPEPs are available, the discovery of miPEPs reveals a new layer of gene regulation at the post-transcriptional level that opens the possibility to regulate plant metabolism without resorting to gene manipulation. Here, we identified a miPEP encoded in non-mature miR164c putatively targeting grapevine transcription factor VvMYBPA1 (miPEP164c/miPEP-MYBPA1), a positive regulator of key genes in the proanthocyanidin (PA)-biosynthetic pathway, a pathway that competes directly for substrate with the anthocyanin-biosynthetic pathway. Thus, the objective of this work was to test the hypothesis that the exogenous application of miPEP164c (miPEP-MYBPA1) can modulate the secondary metabolism of grape berry cells by inhibiting PA biosynthetic pathway while simultaneously stimulating anthocyanin synthesis. The exogenous application of miPEP164c to suspension-cultured cells from grape berry (cv. Gamay) enhanced the transcription of its corresponding non-mature miR164c, with a maximum effect at 1 µM and after a period of 10 days, thus leading to a more pronounced post-transcriptional silencing of its target VvMYBPA1. This led to a significant inhibition of the PA pathway, mostly via inhibition of leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR) enzymatic activities and VvLAR1 downregulation. In parallel, the anthocyanin-biosynthetic route was stimulated. Anthocyanin content was 31% higher in miPEP164c-treated cells, in agreement with the observed upregulation of VvUFGT1 transcripts and UFGT enzyme activity levels.

Light Microclimate-Driven Changes at Transcriptional Level in Photosynthetic Grape Berry Tissues.

Viticulture practices that change the light distribution in the grapevine canopy can interfere with several physiological mechanisms, such as grape berry photosynthesis and other metabolic pathways, and consequently impact the berry biochemical composition, which is key to the final wine quality. We previously showed that the photosynthetic activity of exocarp and seed tissues from a white cultivar (Alvarinho) was in fact responsive to the light microclimate in the canopy (low and high light, LL and HL, respectively), and that these different light microclimates also led to distinct metabolite profiles, suggesting a berry tissue-specific interlink between photosynthesis and metabolism. In the present work, we analyzed the transcript levels of key genes in exocarps and seed integuments of berries from the same cultivar collected from HL and LL microclimates at three developmental stages, using real-time qPCR. In exocarp, the expression levels of genes involved in carbohydrate metabolism (VvSuSy1), phenylpropanoid (VvPAL1), stilbenoid (VvSTS1), and flavan-3-ol synthesis (VvDFR, VvLAR2, and VvANR) were highest at the green stage. In seeds, the expression of several genes associated with both phenylpropanoid (VvCHS1 and VvCHS3) and flavan-3-ol synthesis (VvDFR and VvLAR2) showed a peak at the véraison stage, whereas that of RuBisCO was maintained up to the mature stage. Overall, the HL microclimate, compared to that of LL, resulted in a higher expression of genes encoding elements associated with both photosynthesis (VvChlSyn and VvRuBisCO), carbohydrate metabolism (VvSPS1), and photoprotection (carotenoid pathways genes) in both tissues. HL also induced the expression of the VvFLS1 gene, which was translated into a higher activity of the FLS enzyme producing flavonol-type flavonoids, whereas the expression of several other flavonoid pathway genes (e.g., VvCHS3, VvSTS1, VvDFR, and VvLDOX) was reduced, suggesting a specific role of flavonols in photoprotection of berries growing in the HL microclimate. This work suggests a possible link at the transcriptional level between berry photosynthesis and pathways of primary and secondary metabolism, and provides relevant information for improving the management of the light microenvironment at canopy level of the grapes.

Metabolomics of Photosynthetically Active Tissues in White Grapes: Effects of Light Microclimate and Stress Mitigation Strategies.

The effects of climate change are becoming a real concern for the viticulture sector, with impacts on both grapevine physiology and the quality of the fresh berries and wine. Short-term mitigation strategies, like foliar kaolin application and smart irrigation regimes, have been implemented to overcome these problems. We previously showed that these strategies also influence the photosynthetic activity of the berries themselves, specifically in the exocarp and seed. In the present work, we assessed the modulating effects of both canopy-light microclimate, kaolin and irrigation treatments on the metabolic profiles of the exocarp and seed, as well as the potential role of berry photosynthesis herein. Berries from the white variety Alvarinho were collected at two contrasting light microclimate positions within the vine canopy (HL-high light and LL-low light) from both irrigated and kaolin-treated plants, and their respective controls, at three fruit developmental stages (green, véraison and mature). Untargeted liquid chromatography mass spectrometry (LCMS) profiling of semi-polar extracts followed by multivariate statistical analysis indicate that both the light microclimate and irrigation influenced the level of a series of phenolic compounds, depending on the ripening stage of the berries. Moreover, untargeted gas chromatography mass spectrometry (GCMS) profiling of polar extracts show that amino acid and sugar levels were influenced mainly by the interaction of irrigation and kaolin treatments. The results reveal that both photosynthetically active berry tissues had a distinct metabolic profile in response to the local light microclimate, which suggests a specific role of photosynthesis in these tissues. A higher light intensity within the canopy mainly increased the supply of carbon precursors to the phenylpropanoid/flavonoid pathway, resulting in increased levels of phenolic compounds in the exocarp, while in seeds, light mostly influenced compounds related to carbon storage and seed development. In addition, our work provides new insights into the influence of abiotic stress mitigation strategies on the composition of exocarps and seeds, which are both important tissues for the quality of grape-derived products.

Plant SWEETs: from sugar transport to plant-pathogen interaction and more unexpected physiological roles.

Sugars Will Eventually be Exported Transporters (SWEETs) have important roles in numerous physiological mechanisms where sugar efflux is critical, including phloem loading, nectar secretion, seed nutrient filling, among other less expected functions. They mediate low affinity and high capacity transport, and in angiosperms this family is composed by 20 paralogs on average. As SWEETs facilitate the efflux of sugars, they are highly susceptible to hijacking by pathogens, making them central players in plant-pathogen interaction. For instance, several species from the Xanthomonas genus are able to upregulate the transcription of SWEET transporters in rice (Oryza sativa), upon the secretion of transcription-activator-like effectors. Other pathogens, such as Botrytis cinerea or Erysiphe necator, are also capable of increasing SWEET expression. However, the opposite behavior has been observed in some cases, as overexpression of the tonoplast AtSWEET2 during Pythium irregulare infection restricted sugar availability to the pathogen, rendering plants more resistant. Therefore, a clear-cut role for SWEET transporters during plant-pathogen interactions has so far been difficult to define, as the metabolic signatures and their regulatory nodes, which decide the susceptibility or resistance responses, remain poorly understood. This fuels the still ongoing scientific question: what roles can SWEETs play during plant-pathogen interaction? Likewise, the roles of SWEET transporters in response to abiotic stresses are little understood. Here, in addition to their relevance in biotic stress, we also provide a small glimpse of SWEETs importance during plant abiotic stress, and briefly debate their importance in the particular case of grapevine (Vitis vinifera) due to its socioeconomic impact.

Lemierre's syndrome: a forgotten life-threatening entity.

Lemierre's syndrome is a very rare but potentially fatal condition. It mainly affects adolescents and young adult males, and usually arises as a serious complication of pharyngitis or peritonsillar abscess. It is characterised by the triad of internal jugular vein septic thrombophlebitis, septic emboli (mostly pulmonary) and the isolation of the agent 'Fusobacterium necrophorum' in sterile fluids. In this report, it is described a case in which the nonspecific and subtle clinic made the diagnosis difficult to reach. In fact, only the dissociation between flu-like symptoms and the presence of significant changes in the blood tests (suggestive of acute bacterial infection), led to the request for imaging tests, which proved to be essential for the final diagnosis and subsequent control of the disease. This case report aims to increase the awareness among Ear, Nose and Throat (ENT) residents, paediatricians and family doctors about the existence of this entity and its potential life-threatening nature.

Tuberculosis as a differential diagnosis of salivary gland malignancy.

Mycobacterial infection of the salivary glands is extremely rare, even in endemic countries. Differential diagnosis with benign or malignant neoplasms is challenging, and treatment is often delayed. We describe the case of a 62-year-old female patient who presented with a 2-month-old complaint of a right preauricular painless swelling. An ultrasound-guided fine-needle aspiration biopsy was performed, with a resulting lymphocytic infiltrate, without clear atypia. MRI demonstrated a lesion with ill-defined contours, described as probably malignant. Because of this mismatch in results, a core biopsy of the main lesion was performed, demonstrating granulomas with central necrosis, with no mycobacteria detected in PCR or culture. As the lesion continued to enlarge, a new biopsy was ordered, and this time Mycobacterium tuberculosis was detected. Treatment with extrapulmonary tuberculosis therapy was initiated. The sensitivity of PCR and culture combined is only 73% in extrapulmonary tuberculosis. A systematic approach may prevent unnecessary surgical interventions.

VvERD6l13 is a grapevine sucrose transporter highly up-regulated in response to infection by Botrytis cinerea and Erysiphe necator.

The Early-Response to Dehydration six-like (ERD6l) is one of the largest families of sugar transporters in plants, however, is also one of the less studied with very few members characterized. In this work, we identified 18 members of the grapevine ERD6l family, analyzed their promoters and putative topology and additionally functionally characterized the member VvERD6l13. VvERD6l13 was strongly up-regulated in grape berries infected with Botrytis cinerea and Erysiphe necator in cv. Trincadeira and Carignan, respectively, suggesting an important role in grape berry-pathogen interaction, as we had hypothesized. In Cabernet Sauvignon Berry suspension cultured cells, VvERD6l13 was also up-regulated, by 4-fold, 48 h after elicitation with mycelium extract of B. cinerea. Besides being expressed in grape berries from various developmental stages, VvERD6l13 is also expressed in leaves, canes, flowers and, noticeably, in roots. Using tobacco and an hxt-null Saccharomyces cerevisiae strain as heterologous expression models, we showed that VvERD6l13 is localized at the plasma membrane and mediates the H+-dependent transport of sucrose (Km = 33 mM) thus confirming VvERD6l13 as a bona fide sugar transporter involved in sugar mobilization in grapevine and transcriptionally induced in response to biotic stress.

Acute vestibular syndrome and hearing loss mimicking labyrinthitis as initial presentation of multiple sclerosis.

Acute vestibular syndrome is most often caused by vestibular neuritis or stroke, although demyelinating diseases may be responsible for 4% of all AVS episodes. The authors present the case of a previously healthy 17-year-old female patient complaining of spontaneous vertigo and right-sided hearing loss. Otoneurological examination suggested a peripheral vestibular cause and video head impulse test revealed a reduced vestibulo-ocular reflex gain. The presence of sensorineural hearing loss raised the suspicion of a central cause and prompted imaging evaluation. A brain MRI evidenced demyelinating lesions in the right middle cerebellar peduncle and the patient was ultimately diagnosed with Multiple Sclerosis.

Sweet Cherry (Prunus avium L.) PaPIP1;4 Is a Functional Aquaporin Upregulated by Pre-Harvest Calcium Treatments that Prevent Cracking.

The involvement of aquaporins in rain-induced sweet cherry (Prunus avium L.) fruit cracking is an important research topic with potential agricultural applications. In the present study, we performed the functional characterization of PaPIP1;4, the most expressed aquaporin in sweet cherry fruit. Field experiments focused on the pre-harvest exogenous application to sweet cherry trees, cultivar Skeena, with a solution of 0.5% CaCl2, which is the most common treatment to prevent cracking. Results show that PaPIP1;4 was mostly expressed in the fruit peduncle, but its steady-state transcript levels were higher in fruits from CaCl2-treated plants than in controls. The transient expression of PaPIP1;4-GFP in tobacco epidermal cells and the overexpression of PaPIP1;4 in YSH1172 yeast mutation showed that PaPIP1;4 is a plasma membrane protein able to transport water and hydrogen peroxide. In this study, we characterized for the first time a plasma membrane sweet cherry aquaporin able to transport water and H2O2 that is upregulated by the pre-harvest exogenous application of CaCl2 supplements.

Management of laryngeal candidiasis: an evidence-based approach for the otolaryngologist.

PURPOSE: The authors aim to review available reports regarding laryngeal candidiasis and describe the existing evidence on the demographics, clinical manifestations, diagnosis, therapeutic options, and outcomes of this infection. METHODS: A review of articles on laryngeal candidiasis was conducted using PubMed® database from its inception through July 2019. RESULTS: Patients were mainly females presenting with complaints of dysphonia and associated gastroesophageal reflux history or inhaled corticosteroids use; although local predisposing factors were common, most patients were immunocompetent. The main anatomical affected subsite was the glottis with the presence of leukoplastic lesions. The diagnostic approach remains controversial, since some authors recommend prompt lesion biopsy and others rely on empirical antifungal treatment that showed effective results regarding symptoms and lesions resolution. CONCLUSION: Laryngeal Candida infection is thought to be a rare condition, with limited available literature. The correct diagnosis is difficult for the otolaryngologist and a high level of suspicion is required. The authors emphasize the need to include this condition into the differential diagnosis in patients with predisposing factors presenting with suspected lesions. In addition, the conservative diagnostic approach with antifungal treatment seems to provide effective outcomes, although comparative clinical studies between diagnostic options are lacking.

Epstein-Barr Virus-Associated With Lymphoepithelial Carcinoma: A Rare Tumor of the Larynx.

Lymphoepithelial carcinoma of the larynx is a rare tumor, as this histological entity is mostly diagnosed in nasopharynx. However, it may be present in other non-nasopharyngeal sites and it is extremely rare in the larynx. The authors present a case of a 59-year-old man who presented to the Otorhinolaryngology-Head and Neck Surgery Department complaining of a long-standing dysphonia, odynophagia, and dysphagia. The clinical examination revealed a laryngeal tumor involving the right epiglottis, right aryepiglottic fold, and ipsilateral false vocal fold. It presented with ispilateral neck lymph node extension. Multiple biopsies of the laryngeal lesion were performed under local anesthesia and the histological examination showed a poorly differentiated squamous cell carcinoma. After discussing the case in a multidisciplinary tumor board, a total laryngectomy with a bilateral neck dissection was performed and the histological specimen showed a lymphoepithelial carcinoma. Although immunostaining with LMP-1 antibody was negative, in situ hybridization for Epstein-Barr virus was positive. He underwent adjuvant chemoradiation. He is now at 9-months follow-up period, with no evidence of disease. Lymphoepithelial carcinoma of the larynx is an extremely rare disease, with an aggressive pattern. Epstein-Barr virus-associated lymphoepithelial carcinoma has been exceptionally reported. A correct diagnosis and close collaboration with pathologist is crucial to achieve the best treatment strategy. We present this case to discuss the clinical and histology findings and the different therapeutic aspects of this uncommon histological subtype carcinoma.

The effects on the acoustic parameters and auditory-perceptive characteristics of voice in children submitted to adenoidectomy with or without tonsillectomy.

OBJECTIVES: To analyse the possible changes on the acoustic parameters and auditory-perceptive characteristics of children's voice after adenoidectomy with or without tonsillectomy. METHODS: Prospective cohort study of children aged 5-12 years at one month before surgery (t0) and one (t1), three (t3) and six (t6) months after adenoidectomy with or without tonsillectomy. On each assessment the acoustic parameters (fundamental frequency, jitter %, shimmer % and harmonics-to-noise ratio) and auditory-perceptive analysis (nasal resonance, loudness, pitch, GRBAS scale and maximum phonation time) were recorded. RESULTS: A total of 51 children were considered for data analysis. Nasal resonance revealed a significant decrease in the number of cases with hyponasality, from 86.3% at t0 to 12.8% at t1 (p < 0.001), 2.3% at t3 (p < 0.001) and 2.8% at t6 (p < 0.001). This improvement was maintained during the late follow-up time with no significant difference on nasal resonance between t0 and t3 (p = 0.250) and t3 and t6 (p = 0.250). All children with alteration on the GRBAS scale before the procedure showed a normal voice quality after the surgery. Regarding the acoustic parameters none showed a significant change with the surgery. CONCLUSIONS: The results suggest that adenoidectomy with or without tonsillectomy is a safe procedure concerning voice alterations and can improve voice quality and nasal resonance in a sustained manner.

Vernet syndrome: intracranial extension of a slow-growing mass.

Vernet syndrome, often referred to as jugular foramen syndrome, is a rare clinical entity characterised by a set of signs and symptoms caused by dysfunction of IX, X and XI cranial nerves. Although paraganglioma of the head and neck is the most frequent aetiology, it may also be caused by meningioma, VIII cranial nerve schwannoma, pontocerebellar cistern metastases, head and neck trauma, infections and very rarely by cholesteatoma which extends to the petrous apex. The authors describe a case of a patient with a jugulotympanic paraganglioma in which evolution ends up in Vernet syndrome. The patient preferred a 'wait and scan' strategy. With the lack of data available to develop an unequivocal algorithm for paraganglioma management, we always consider not only age but also comorbidities, prior treatment and progression of the lesion. Each case has to be addressed individually and treatment should be discussed in detail with every patient.